Neoadjuvant Short-Course Radiotherapy Plus Tislelizumab and Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

NCT07678580 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT202601-03-KYB-03-XW
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant Short-Course Radiotherapy Followed by Tislelizumab Plus Chemotherapy for Locally Advanced Resectable Esophageal Squamous Cell Carcinoma This is a prospective, randomized, two-arm, parallel-group, multicenter, exploratory Phase II clinical trial. It aims to evaluate the efficacy and safety of neoadjuvant short-course radiotherapy followed by tislelizumab combined with chemotherapy in participants with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Eligible participants will be randomized in a 1:1 ratio to receive either low-dose or high-dose short-course radiotherapy, followed by tislelizumab, nab-paclitaxel, and carboplatin for 3 cycles. Surgery will be performed 4-6 weeks after the last neoadjuvant treatment. Primary endpoint: Pathological Complete Response (pCR) rate. Secondary endpoints: Major Pathological Response (MPR) rate, Objective Response Rate (ORR), R0 resection rate, downstaging rate, 3-year Event-Free Survival (EFS), 3-year Overall Survival (OS), safety profile, and quality of life. Approximately 50 participants will be enrolled. Randomization will be stratified by tumor location, clinical T stage, and clinical N stage using a stratified block design via an EDC/IWRS system.

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Keywords

Esophageal Squamous Cell Carcinoma; Neoadjuvant Therapy; Short-Course Radiotherapy; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  The primary outcome measure is the rate of pathological complete response (pCR) after completion of neoadjuvant treatment. Pathological complete response is defined as the absence of residual invasive cancer cells in the primary esophageal tumor bed and all sampled regional lymph nodes, confirmed by postoperative pathological examination by a qualified pathologist.

  Within 1 week after surgical resection.

Secondary Outcomes (7)

• Major Pathological Response(MPR) Rate

  Within 1 week after surgical resection

• R0 Resection Rate

  At the time of surgical resection

• Incidence of Treatment-Related Adverse Events (CTCAE v5.0)

  From start of neoadjuvant treatment through 30 days after last study treatment

• Objective Response Rate (ORR)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to surgical resection

• 3-Year Event-Free Survival (EFS) Rate

  Followed up for up to 3 years from the date of randomization.

Study Arms (2)

Low-Dose Radiotherapy + Tislelizumab + Chemotherapy

EXPERIMENTAL

Neoadjuvant low-dose short-course radiotherapy (10 Gy in 5 fractions) followed by tislelizumab combined with nab-paclitaxel and carboplatin for 3 cycles, then surgical resection.

Drug: Albumin-bound paclitaxel; Radiation: Low-dose Short-course Radiotherapy; Drug: Tislelizumab Combined With Chemotherapy for 3 cycles; Drug: Carboplatin (AUC 5)

High-Dose Radiotherapy + Tislelizumab + Chemotherapy

EXPERIMENTAL

Neoadjuvant high-dose short-course radiotherapy (15 Gy in 5 fractions) followed by tislelizumab combined with nab-paclitaxel and carboplatin for 3 cycles, then surgical resection.

Drug: Albumin-bound paclitaxel; Radiation: High-dose Short-course Radiotherapy; Drug: Tislelizumab Combined With Chemotherapy for 3 cycles; Drug: Carboplatin (AUC 5)

Interventions

Albumin-bound paclitaxel DRUG

Albumin-bound paclitaxel at a dose of 125 mg/m² is administrated intravenously on day 1 and day 8 of each 3-week cycle, for a total of 3 cycles.

High-Dose Radiotherapy + Tislelizumab + Chemotherapy; Low-Dose Radiotherapy + Tislelizumab + Chemotherapy

Low-dose Short-course Radiotherapy RADIATION

Neoadjuvant short-course radiotherapy with a total dose of 10 Gy, delivered in 5 daily fractions of 2.0 Gy per fraction, administered consecutively before systemic combination therapy.

Low-Dose Radiotherapy + Tislelizumab + Chemotherapy

High-dose Short-course Radiotherapy RADIATION

Neoadjuvant short-course radiotherapy with a total dose of 15 Gy, delivered in 5 daily fractions of 3.0 Gy per fraction, administered consecutively before systemic combination therapy.

High-Dose Radiotherapy + Tislelizumab + Chemotherapy

Tislelizumab Combined With Chemotherapy for 3 cycles DRUG

Anti-PD-1 monoclonal antibody tislelizumab 200 mg is given by intravenous infusion on day 1 of each 3-week cycle, for up to 3 cycles in the neoadjuvant treatment phase.

High-Dose Radiotherapy + Tislelizumab + Chemotherapy; Low-Dose Radiotherapy + Tislelizumab + Chemotherapy

Carboplatin (AUC 5) DRUG

Carboplatin is given intravenously on day 1 of each cycle at a targeted AUC of 5, repeated every 3 weeks for 3 cycles as part of neoadjuvant combination regimen.

High-Dose Radiotherapy + Tislelizumab + Chemotherapy; Low-Dose Radiotherapy + Tislelizumab + Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily provided written informed consent prior to any study-related procedures
• Aged 18 to 75 years, male or female
• Life expectancy of at least 3 months
• Predicted to achieve R0 surgical resection
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically confirmed, treatment-naive, resectable locally advanced thoracic esophageal squamous cell carcinoma (ESCC) meeting the staging criteria: T1 N1-3 M0 or T2-4a N0-3 M0 (T2 ≥3 cm or poorly differentiated). No suspected metastatic cervical lymph nodes (except for upper thoracic esophageal cancer regional lymph nodes) on neck ultrasound or contrast-enhanced CT, and no distant metastasis on imaging
• Presence of measurable tumor lesions.
• Adequate organ function defined by laboratory parameters: Absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count ≥100×10⁹/L; hemoglobin ≥90 g/L. Total bilirubin ≤1.5×ULN; AST and ALT ≤2.5×ULN. Serum creatinine ≤1.5×ULN or calculated creatinine clearance ≥60 mL/min. INR ≤1.5, PT and APTT ≤1.5×ULN
• Men and women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose of study treatment
• Good compliance and ability to complete scheduled follow-up.

You may not qualify if:

• Prior treatment with PD-1/PD-L1 inhibitors or other immunomodulatory agents targeting T-cell receptors (e.g., CTLA-4, OX40)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage
• Active or suspected autoimmune disease, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, except type 1 diabetes controlled by replacement therapy, hypothyroidism, or skin disorders not requiring systemic therapy
• History of grade ≥2 interstitial lung disease
• Systemic corticosteroids (\>10 mg prednisone daily or equivalent) or other immunosuppressive agents within 14 days before first study treatment
• Primary or acquired immunodeficiency, organ transplantation, allogeneic hematopoietic stem cell transplantation
• Live vaccine within 4 weeks before first study treatment
• Severe uncontrolled cardiovascular or cerebrovascular disease: Uncontrolled hypertension or pulmonary hypertension. Unstable angina, myocardial infarction, coronary artery bypass grafting, or stent implantation within 6 months. NYHA class ≥2 chronic heart failure. Left ventricular ejection fraction (LVEF) \<50%.
• Clinically significant arrhythmia requiring treatment. Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months. Uncontrolled active infection requiring systemic antibiotics. Positive HIV test, active hepatitis B or hepatitis C infection (exceptions: HBV DNA \<500 IU/mL; HCV RNA undetectable).
• Active pulmonary tuberculosis (TB). Other active malignancy within the previous 2 years, except adequately treated thyroid cancer, carcinoma in situ of the cervix, basal/squamous cell skin cancer, or ductal carcinoma in situ of the breast
• History of drug abuse or psychiatric disorder
• Pregnant or lactating women
• Any other severe medical, psychiatric, or laboratory abnormality that, in the investigator's opinion, would increase study-related risk or interfere with result interpretation.

Sponsors & Collaborators

• Tang-Du Hospital: lead

Study Sites (1)

Tangdu Hospital, Fourth Military Medical University

Xi'an, Shaanxi, 710038, China

Location

Related Publications (3)

• Li C, Han Y, Zhao S, Kang X, Zheng Y, Cao Y, Yan Y, Shi L, Wang X, Lu T, Zou G, Li H, Che J, Xiang J, Zhu L, Hang J, Zhang Y, Jin R, Han D, Chen X, Jing H, Guo W, Cheng Z, Zhao L, Chen X, Yu B, Li J, Li B, Li Y, Li H. Preoperative pembrolizumab (anti-PD-1 antibody) combined with chemoradiotherapy for esophageal squamous cell carcinoma: a phase 1/2 trial (PALACE-2). Signal Transduct Target Ther. 2025 Nov 28;10(1):386. doi: 10.1038/s41392-025-02477-4.

  PMID: 41309527 RESULT

• Ghalehtaki R, Amini A, Abyaneh R. Optimizing neoadjuvant radiotherapy for locally advanced esophageal squamous cell carcinoma: a comprehensive review on the role of concomitant or sequential immune checkpoint inhibitors. Esophagus. 2025 Jan;22(1):5-18. doi: 10.1007/s10388-024-01097-1. Epub 2024 Nov 19.

  PMID: 39562407 RESULT

• He W, Bai H, Lv J, Tang P, Hu T, Zhou H, Xiao W, Peng L, Liu G, Wang K, Fang Q, Qi Y, Liang L, Zheng X, Qing H, Chen Y, Zhou Y, Xie W, Han Y, Leng X. Neoadjuvant chemotherapy or chemoradiotherapy plus sintilimab versus neoadjuvant chemoradiotherapy for locally advanced oesophageal squamous cell carcinoma: a study protocol of a multicentre, randomised, controlled, phase III trial (SCIENCE study). BMJ Open. 2025 Jun 4;15(6):e095828. doi: 10.1136/bmjopen-2024-095828.

  PMID: 40467307 RESULT

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Interventions

Albumin-Bound Paclitaxel; Drug Therapy; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Therapeutics; Coordination Complexes

Central Study Contacts

Xiaolong Yan, Doctor

CONTACT

029-84717551; 18710959981@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomly assigned in a 1:1 ratio to one of two parallel treatment groups: Group A (low-dose short-course radiotherapy followed by tislelizumab plus chemotherapy) or Group B (high-dose short-course radiotherapy followed by tislelizumab plus chemotherapy). All participants will receive the same subsequent surgical treatment and follow-up schedule.

Study Record Dates

• First Submitted: May 24, 2026
• First Posted: July 1, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: July 1, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)